The mouse thymic/lymphoma models resemble certain types of childhood acute lymphoblastic leukemia. The disease arises in the thymus gland which is the central organ in the body for development of bone marrow precrsors into mature thymus-derived lymphocytes (T cells) capable of mediating specific immunity against virus, bacteria, and cancer cells. Development of spontaneous lymphoma in the AKR strain of mouse is associated with life long expression of endogenous ecotropic murine leukemia virus (MuLV). Recent evidence has indicated the latent expression of a recombinant MuLV as the oncogenic entity . However, direct malignant transformation of normal T cells by MuLV has not been demonstrated. Thus an alternative explanation is sought. In the present proposal an indirect effect of oncogenic MuLV in leukemogeneisis is hypothesized. It is possible that oncogenic MuLV causes an alteration in the proper maturation and differentiation of T cells, resulting in an imbalance in the immune system which then leads to malignancy. It is assumed that any defect is subtle. Therefore, it is proposed to use more refined immunological techniques to study the effects of oncogenic MuLV on matuation and differentiation of T cells. A very sensitive assay for thymopoitic production will be used to measure the effect of oncogenic MuLV upon thymic epithelium. The influence of virus on cooperative function of helper T cells eliciting a secondary humoral immune response will be examined. Finally, variable susceptibility to cell mediated lympholysis (CML) of lymphoma cells depending on expression of oncogenic MuLV will be measured. An alteration in any of these three levels of maturation and differentiation of T cell function could trigger malignancy,